Combinatorial approaches toward the development of efficient copper-catalyzed aromatic substitution reactions

Samenvatting

The formation of aryl C–X (X = N, O) bonds via aromatic substitution reactions represents a powerful method for the preparation of numerous products important in pharmaceutical, biological, agrochemical and material sciences. Efficient palladium-catalyzed aminations and etherifications were developed in recent years and were proven to be useful in both academic and industrial laboratories. However, significant limitations still exist: (i) palladium-based methods are often relatively sensitive to oxygen and moisture, (ii) certain functional groups directly bound to the aryl halide prove to be problematic, and (iii) the use of palladium and phosphine or related ligands limit the attractiveness for certain applications. The aim of this proposal is to develop aromatic substitution procedures where expensive noble metal catalysts are replaced by cheap, stable, commercially available and toxicologically benign copper catalysts. In this study important parameters will be varied to prepare the different ligands; (i) electron-donating and withdrawing abilities of the ligands (s and p). (ii) the sterics around the donating atom on the ligands, (iii) monodentate or multidentate donation (with variation in ligand bite angles), and (iv) variation of the organic backbone (alkyl ligand). For the screening of homogeneous copper-catalyzed reactions several parameters can be varied such as (in random order): ligand, metal-to-ligand ratio, method of catalyst preparation, substrate-to-catalyst ratio, reactant, solvent, temperature, pressure, concentration of catalyst, substrate and reactants, order of mixing, additives such as bases, and other parameters. By parallel automated synthesis methods all these different parameters will be tested. Examination of the experimental data leads to the rational design of new copper catalysts, which will be synthesized and tested in aromatic substitution reactions. The ultimate aim is to synthesize a new generation of stable, copper-based catalysts that are active at catalytic amounts.

Kenmerken

Projectnummer

700.52.603

Hoofdaanvrager

Dr. G.P.M. van Klink

Verbonden aan

Technische Universiteit Delft, Faculteit Technische Natuurwetenschappen, Chemical Engineering

Uitvoerders

Dr. T. Jerphagnon, Mw. E. Sperotto MSc

Looptijd

01/04/2004 tot 28/11/2008